Melatonin attenuates choroidal neovascularization by regulating macrophage/microglia polarization via inhibition of RhoA/ROCK signaling pathway
Melatonin attenuates choroidal neovascularization by regulating macrophage/microglia polarization via inhibition of RhoA/ROCK signaling pathway
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褪黑素通过抑制 RhoA/ROCK 信号通路调节巨噬细胞/小胶质细胞极化，从而减弱脉络膜新生血管形成
DOI：
10.1111/jpi.12660
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发表时间：
2020-04
影响因子：
10.3
通讯作者：
Liang Xiaoling
中科院分区：
文献类型：
--
作者：
Xu Yue;Cui Kaixuan;Li Jia;Tang Xiaoyu;Lin Jianqiang;Lu Xi;Huang Rong;Yang Boyu;Shi Yuxun;Ye Dan;Huang Jingjing;Yu Shanshan;Liang Xiaoling
脉络膜新生血管（CNV）是晚期湿性年龄相关性黄斑变性（AMD）的一个重要特征，在老年患者中导致严重的视力损害。先前的研究表明，褪黑素诱导了几种与抗氧化、抗炎症和抗血管生成有关的生物学效应。然而，褪黑素在CNV中的作用及其潜在机制迄今尚未得到研究。在本研究中，我们发现在激光诱导的小鼠CNV模型中，褪黑激素的使用显著降低了CNV病变的规模和体积，抑制了血管渗漏，并抑制了血管增殖能力。此外，研究结果还表明，褪黑素处理的激光诱导小鼠视网膜小胶质细胞中，M1型标记物（如iNOS、CCL-3、CCL-5和tnf - α）的表达增强，M2型标记物（如Arg-1、Fizz-1、IL-10、m -1和CD206）的表达减少，表明褪黑素将巨噬细胞/小胶质细胞极化从促血管生成M2表型转变为抗血管生成M1表型。此外，RhoA/ROCK信号通路在CNV形成过程中被激活，但在腹腔注射褪黑激素后被抑制。综上所述，褪黑激素通过抑制CNV中的RhoA/ROCK信号通路，将巨噬细胞/小胶质细胞的极化从M2表型转变为M1表型，从而减弱CNV，减少血管渗漏，抑制血管增殖。这表明褪黑素可能是一种治疗AMD的新药物。
Choroidal neovascularization (CNV) is an important characteristic of advanced wet age-related macular degeneration (AMD) and leads to severe visual impairment among elderly patients. Previous studies have demonstrated that melatonin induces several biological effects related to antioxidation, anti-inflammation, and anti-angiogenesis. However, the role of melatonin in CNV, and its underlying mechanisms, has not been investigated thus far. In this study, we found that melatonin administration significantly reduced the scale and volume of CNV lesions, suppressed vascular leakage, and inhibited the capacity of vascular proliferation in the laser-induced mouse CNV model. Additionally, the results also show that the melatonin-treated retinal microglia in the laser-induced mice exhibited enhanced expression of M1-type markers, such as iNOS, CCL-3, CCL-5, and TNF-alpha, as well as decreased production of M2-type markers, such as Arg-1, Fizz-1, IL-10, YM-1, and CD206, indicating that melatonin switched the macrophage/microglia polarization from pro-angiogenic M2 phenotype to anti-angiogenic M1 phenotype. Furthermore, the RhoA/ROCK signaling pathway was activated during CNV formation, yet was suppressed after an intraperitoneal injection of melatonin. In conclusion, melatonin attenuated CNV, reduced vascular leakage, and inhibited vascular proliferation by switching the macrophage/microglia polarization from M2 phenotype to M1 phenotype via inhibition of RhoA/ROCK signaling pathway in CNV. This suggests that melatonin could be a novel agent for the treatment of AMD.
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影响因子：
--
作者：
Hernández-Zimbrón LF;Zamora-Alvarado R;Ochoa-De la Paz L;Velez-Montoya R;Zenteno E;Gulias-Cañizo R;Quiroz-Mercado H;Gonzalez-Salinas R
通讯作者：
Gonzalez-Salinas R
影响因子：
10.3
作者：
Borin TF;Arbab AS;Gelaleti GB;Ferreira LC;Moschetta MG;Jardim-Perassi BV;Iskander AS;Varma NR;Shankar A;Coimbra VB;Fabri VA;de Oliveira JG;Zuccari DA
通讯作者：
Zuccari DA
影响因子：
15.8
作者：
Apte, Rajendra S.;Richter, Jennifer;Herndon, John;Ferguson, Thomas A.
通讯作者：
Ferguson, Thomas A.
影响因子：
3.4
作者：
Tosini, Gianluca;Baba, Kenkichi;Hwang, Christopher K.;Iuvone, P. Michael
通讯作者：
Iuvone, P. Michael
rd1 小鼠视网膜变性模型中小胶质细胞极化与 M1/M2 表型变化
影响因子：
2.9
作者：
Zhou Tian;Huang Zijing;Sun Xiaowei;Zhu Xiaowei;Zhou Lingli;Li Mei;Cheng Bing;Liu Xialin;He Chang
通讯作者：
He Chang